Compositions and methods for dengue virus chimeric constructions in vaccines

A modified live, attenuated dengue-2 virus strain PDK-53, wherein the modified live, attenuated dengue-2 virus strain PDK-53 comprises an RNA transcribed from a cDNA comprising a polynucleotide molecule encoding the modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule, wherein the polynucleotide molecule encoding the modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule comprises at least one mutation, wherein the at least one mutation comprises:

• an adenine to guanine mutation at position 592 in the numbering of SEQ ID NO:
• 14 encoding a glutamic acid instead of a lysine in the polypeptide molecule at amino acid position 166 in the numbering of SEQ ID NO:
• 6 corresponding to prM-52, and
• an adenine to guanine mutation at position 8803 in the numbering of SEQ ID NO:
• 14 encoding a valine instead of an isoleucine in the polypeptide molecule at amino acid position 2903 in the numbering of SEQ ID NO:
• 6 corresponding to NS5-412.

A modified live, attenuated dengue-2 virus strain PDK-53, wherein the modified live, attenuated dengue-2 virus strain PDK-53 comprises one or more polypeptide molecules encoded by a polynucleotide molecule encoding the modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule,

• wherein the polynucleotide molecule encoding the modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule comprises at least one mutation, wherein the at least one mutation comprises:
• an adenine to guanine mutation at position 592 in the numbering of SEQ ID NO:
• 14 encoding a glutamic acid instead of a lysine in the polypeptide molecule at amino acid position 166 in the numbering of SEQ ID NO:
• 6 corresponding to prM-52, and
• an adenine to guanine mutation at position 8803 in the numbering of SEQ ID NO:
• 14 encoding a valine instead of an isoleucine in the polypeptide molecule at amino acid position 2903 in the numbering of SEQ ID NO:
• 6 corresponding to NS5-412.

A modified live, attenuated dengue-2 virus strain PDK-53, wherein the modified live, attenuated dengue-2 virus strain PDK-53 is obtainable by a method for producing a modified live, attenuated dengue-2 virus strain PDK-53, the method comprising the following steps:

• a) transcribing an RNA from a cDNA comprising a polynucleotide molecule encoding the modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule, and
• b) introducing the RNA transcribed in step a) into cells for production of the modified live, attenuated dengue-2 virus strain PDK-53,
• wherein the polynucleotide molecule encoding the modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule comprises at least one mutation, wherein the at least one mutation comprises:
• an adenine to guanine mutation at position 592 in the numbering of SEQ ID NO:
• 14 encoding a glutamic acid instead of a lysine in the polypeptide molecule at amino acid position 166 in the numbering of SEQ ID NO:
• 6 corresponding to prM-52, and
• an adenine to guanine mutation at position 8803 in the numbering of SEQ ID NO:
• 14 encoding a valine instead of an isoleucine in the polypeptide molecule at amino acid position 2903 in the numbering of SEQ ID NO:
• 6 corresponding to NS5-412.